Results obtained indicated that under defined conditions (Nature 275: 60-62, 1978), three carcinogens, N-methyl-N-nitrosourea (MNU), dimethylnitrosamine (DMN) and diethylnitrosamine, given at non-necrogenic doses, induced islands of putative preneoplastic hepatocytes positive for gamma-glutamyl transpeptidase in rat liver when the rats were subjected to a liver cell proliferation stimulus such as partial hepatectomy (PH) after the administration of the carcinogen. Very few or no foci were seen in control groups such as carcinogen plus sham hepatectomy and vehicle plus PH. These results suggested that cell proliferation and possibly replication of carcinogen-damaged DNA may be an obligatory step in the induction of preneoplastic hepatocytes. Experiments are in progress to determine whether these islands of putative preneoplastic hepatocytes induced by MNU and DMN progress eventually into cancer. Experiments are also in progress to identify the lesion(s) in liver DNA induced by MNU responsible for the induction of preneoplastic and neoplastic hepatocyte populations.